Detection of pleural effusion using transthoracic impedance

ABSTRACT

This patent document discusses systems, devices, and methods for increasing a sensitivity or specificity of thoracic fluid detection in a subject and differentiating between pleural effusion and pulmonary edema. In one example, a thoracic impedance measurement circuit senses a thoracic impedance signal. In another example, a processor receives the thoracic impedance signal and determines whether such thoracic impedance signal is “significant.” A significant thoracic impedance signal indicates the presence of thoracic fluid and may be recognized by comparing the thoracic impedance signal (or variation thereof) to a thoracic impedance threshold. When a significant thoracic impedance signal is recognized, the processor is adapted to detect one or both of: a pleural effusion indication and a pulmonary edema indication using one or a combination of: physiologic information, patient symptom information, and posture information. In another example, the thoracic impedance threshold is adjusted using such physiologic, patient symptom, or posture information.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/132,109, filed on May 18, 2005, which is now issued as U.S. Pat. No.7,340,296, the specification of which is incorporated herein byreference in its entirety.

TECHNICAL FIELD

This patent document pertains generally to medical systems, devices, andmethods, and more particularly, but not by way of limitation, tothoracic fluid detection.

BACKGROUND

Variations in how much fluid is present in a person's thorax can takevarious forms and can have different causes. For example, eating saltyfoods can result in retaining excessive fluid in the thorax, which iscommonly referred to as “thoracic fluid,” and elsewhere. Posture changescan also affect the amount of thoracic fluid present at a given time.For example, moving from a supine to standing position can shiftintravascular fluid away from the thorax, toward the lower extremities.

Another cause of fluid build-up in a person's thorax is pulmonary edema,which involves buildup of extravascular fluid in the lungs. In pulmonaryedema, fluid accumulates in extracellular spaces, such as the spacesbetween lung tissue cells. One cause of pulmonary edema is congestiveheart failure (CHF), which is also sometimes referred to as “chronicheart failure” or simply as “heart failure.” In many situations, CHF canbe conceptualized as an enlarged weakened portion of heart muscle. Theimpaired heart muscle results in poor cardiac output of blood. As aresult of the impaired heart muscle, fluid tends to pool in bloodvessels in the lungs and becomes a barrier to normal oxygen exchange.This intravascular fluid buildup, in turn, results in the extravascularfluid buildup mentioned above. Accordingly, pulmonary edema may be anindicative and important condition associated with CHF.

Yet another example of thoracic fluid accumulation is pleural effusion,which is the buildup of extravascular fluid in the space between thelungs and the rib cage. The lungs are covered by a membrane called thepleura, which has two layers, an inner layer and an outer layer. Theouter layer lines the rib cage and diaphragm. The inner layer covers thelungs. The pleura produces a fluid, which acts as a lubricant to help inbreathing, allowing the lungs to move in and out smoothly. Pleuraleffusion is the accumulation of too much of such fluid. Pleuraleffusion, like pulmonary edema, may also result from CHF and provide an(early) indication that heart failure is present or has worsened.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe similar components throughout the several views. The drawingsillustrate generally, by way of example, but not by way of limitation,various embodiments discussed in the present document.

FIG. 1 is a schematic view illustrating a system comprising animplantable medical device (IMD) and one or more of external userinterface communicable with the IMD, the system is adapted to detect thepresence of thoracic fluid in a subject and determine the existence ofone or both of: a pleural effusion indication and a pulmonary edemaindication.

FIG. 2 is a schematic view illustrating an IMD for use in a systemadapted to detect the presence of thoracic fluid in a subject anddetermine the existence of one or a combination of: a pleural effusionindication and a pulmonary edema indication.

FIG. 3 is a schematic diagram illustrating a portion of a system adaptedto detect the presence of thoracic fluid in a subject and determine theexistence of one or a combination of: a pleural effusion indication anda pulmonary edema indication.

FIG. 4 is a flow chart including exemplary factors which may be used todifferentiate a pleural effusion indication and a pulmonary edemaindication.

FIG. 5 is a graph illustrating an increase in sensitivity of thoracicfluid detection performed by the present systems, devices, and methods.

FIG. 6 is a flow chart illustrating one method of detecting the presenceof thoracic fluid in a subject and determining the existence of one or acombination of: a pleural effusion indication and a pulmonary edemaindication.

FIG. 7 is a flow chart illustrating one method of increasing asensitivity of thoracic fluid detection in a subject and detecting oneor a combination of: a pleural effusion indication and a pulmonary edemaindication.

DETAILED DESCRIPTION

The following detailed description includes references to theaccompanying drawings, which form a part of this detailed description.The drawings show, by way of illustration, specific embodiments in whichthe present systems, devices, and methods may be practiced. Theseembodiments, which are also referred to herein as “examples,” aredescribed in enough detail to enable those skilled in the art topractice the present systems, devices, and methods. The embodiments maybe combined or varied, other embodiments may be utilized, or structural,logical or electrical changes may be made without departing from thescope of the present systems, devices, and methods. It is also to beunderstood that the various embodiments of the present systems, devices,and methods, although different, are not necessarily mutually exclusive.For example, a particular feature, structure or characteristic describedin one embodiment may be included within other embodiments. Thefollowing detailed description is, therefore, not to be taken in alimiting sense, and the scope of the present systems, devices, andmethods are defined by the appended claims and their equivalents.

In this document: the terms “a” or “an” are used to include one or morethan one; the term “or” is used to refer to a nonexclusive or, unlessotherwise indicated; the terms “near-DC thoracic impedance signal(s)”(or simply “near-DC component”) are defined to include thoracicimpedance signals at frequencies less than the frequencies at whichcardiac stroke and respiration components (of thoracic impedancesignals) lie, which is typically understood to include signalfrequencies from 0 Hz to about 0.05 Hz, inclusive (e.g., cardiac strokeand respiration components of thoracic impedance signals lie atfrequencies greater than 0.05 Hz); the term “intravascular” includes theterm “intracardiac”; the term “thorax” refers to a human subject's bodybetween the neck and diaphragm; the term “subject” is used synonymouslywith the term “patient”; the term “user” includes a caregiver, asubject, a loved one or others who may ascertain or provide physiologicinformation, patient symptom information, or posture information to thepresent systems, devices, and methods; the term “treatment” includes,among other things, a therapy directed to an underlying cause of athoracic fluid build-up or the thoracic fluid build-up itself; themeaning of the term “detect” includes “determining the existence of”;and the meaning of the phrase “significant thoracic impedance signal”includes a thoracic impedance signal numerically less than, orsubstantially equal to, a thoracic impedance threshold value.

Furthermore, all publications, patents, and patent documents referred toin this document are incorporated by reference herein in their entirety,as though individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated referencesshould be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

Introduction

Today, heart failure is a major cause of hospital admissions in theUnited States as it contributes to more than 4 million hospitalizationsper year. According to recent statistics, hospitalizations for heartfailure cost upwards of 12 billion dollars per year. Many of thesehospital admissions are due to (excessive) fluid accumulation in thethorax of subjects, which is challenging to treat and often goesundetected until such subjects are critically ill. It is estimated thatin the United States, pleural effusion affects 1.3 million people eachyear.

Morbidity and mortality of heart failure can potentially be lowered withaccurate detection and appropriate treatment of the disease in its earlystages. As mentioned above, both pleural effusion and pulmonary edemamay provide an (early) indication of heart failure. Thus, the detectionof pleural effusion or pulmonary edema may reduce or eliminate the needfor subjects with heart failure to require hospital admission. Areduction or elimination of the need for hospitalization results inlower health care costs.

EXAMPLES

Detection of both pleural effusion and pulmonary edema may be made bymonitoring an impedance of a subject's thoracic cavity. In each case, areduction in thoracic impedance indicates the presence of an increase inthoracic fluid. Conversely, fluid depletion in the thorax corresponds toan increase in the thoracic impedance detected. In pleural effusion, areduction in thoracic impedance indicates an increase in the amount offluid between the pleural membranes outside the subject's lungs. Inpulmonary edema, a reduction in thoracic impedance indicates an increasein the amount of fluid inside the subject's lungs. Since reducedthoracic impedance will occur with either of pleural effusion andpulmonary edema, differential detection of these conditions may beuseful. One example of such usefulness arises from the fact thattreatment requirements (e.g., therapy) may differ depending on whetherpleural effusion or pulmonary edema or both are responsible for areduction in thoracic impedance sensed.

The present systems, devices, and methods may differentiate pleuraleffusion and pulmonary edema using, in addition to sensed thoracicimpedance, one or a combination of: physiological information, patientsymptom information, and posture information. The present inventors haverecognized that while some patient symptoms (e.g., dyspnea) may beassociated with both pleural effusion and pulmonary edema, other patientsymptoms (e.g., a pleuritic chest pain or one or more hiccups) areunique to pleural effusion. The present inventors have also recognizedthat sensed thoracic impedance may change at a greater rate with achange in posture orientation when pleural effusion is present than whenpulmonary edema is present. Further, the present inventors haverecognized that physiologic information (e.g., one or more respiratorysounds) may also be useful in differentiating pleural effusion andpulmonary edema.

The present systems, devices, and methods may also advantageouslyimprove a “sensitivity” or a “specificity” of thoracic fluid detectionusing, at least in part, the physiologic information, the patientsymptom information, or the posture information. Sensitivity generallyrefers to the ability of a detection scheme to effectively detect thatwhich a user desires to detect or treat. Specificity generally refers tothe ability of a detection scheme to avoid erroneous or “false”detections of that which a user desires to detect or treat. The desirefor an effective detection system generally involves a tradeoff betweensensitivity and specificity, both of which must be simultaneouslyadequate to ensure acceptable detection system performance. As discussedbelow, when the physiologic information, the patient symptominformation, or the posture information point toward the presence ofthoracic fluid, a base thoracic impedance threshold is adjusted(improving sensitivity or specificity) to account for such information.

The techniques for detecting thoracic fluid and differentiating betweenpleural effusion and pulmonary edema, as described herein, may beimplemented in an IMD adapted to perform detection and differentiationonly or in an IMD configured to also deliver a therapy. In one example,the IMD is a cardiac rhythm management (CRM) device adapted to providebradycardia pacing therapy, cardioversion/defibrillation therapy, drugtherapy, or cardiac resynchronization therapy. Such therapy may beparticularly useful since heart failure subjects with pleural effusionor pulmonary edema may also benefit from, for example, resynchronizationpacing which can improve cardiac function by causing the ventricles of asubject's heart to contract in a more coordinated manner. Examples ofresynchronization devices are described in Kramer, et al., U.S. Pat. No.6,574,506, entitled “SYSTEM AND METHOD FOR TIMING SYNCHRONIZED PACING,”assigned to Cardiac Pacemakers, Inc., and hereby incorporated byreference in its entirety.

This patent document discusses, among other things, systems, devices,and methods that will be described in applications involving IMDsincluding, but not limited to, implantable CRM systems such aspacemakers, cardioverter/defibrillators, pacer/defibrillators,biventricular or other multi-site resynchronization or coordinationdevices, and drug delivery systems. However, the systems, devices, andmethods described herein may also be employed in unimplanted devices,including, but not limited to, external pacemakers,cardioverter/defibrillators, pacer/defibrillators, biventricular orother multi-site resynchronization or coordination devices, monitors,programmers and recorders, whether such devices are used for providingdetection, differentiation, or therapy.

FIG. 1 is a schematic view illustrating generally, by way of example, asystem 100 capable of detecting the presence of thoracic fluid anddetermining the existence of one or a combination of: a pleural effusionindication and a pulmonary edema indication using, in addition to sensedthoracic impedance, physiologic information, patient symptominformation, or posture information. In this example, the system 100includes an implantable medical device (IMD) 102, such as a cardiacrhythm management (CRM) device, and one or more external user interfaces104, 106. IMD 102 may be a battery-powered device that is implantedsubcutaneously in a subject's chest or elsewhere and connected toelectrodes associated with the subject's heart 112 by one or moreleadwires 108. In this example, at least one external user interface 104or 106 is configured to wirelessly communicate with IMD 102. As anexample, IMD 102 may communicate with external user interface 104 orother device (which is typically nearby), or with external userinterface 106 or other device (which is typically distant), via Internet110 or other communication modality.

In varying examples, at least one external user interface 104 or 106includes a user input device 114 or 116, respectively. Each user inputdevice 114 or 116 may be configured to collect physiologic information(e.g., a deemed indication of one or more respiratory sounds), patientsymptom information (e.g., a deemed presence or severity of pleuriticchest pain or a deemed intensity or frequency of one or more hiccups),or posture information (e.g., an indication of a supine or standingposition) from a user. In one example, the user input device 114 or 116functions as a physiologic information device into which the user canenter physiologic information about the subject. In another example, theuser input device 114 or 116 functions as a patient symptom device intowhich the user can enter patient symptom information about the subject.In yet another example, the user input device 114 or 116 functions as aposture information device into which the user can enter postureinformation (such as a thoracic orientation from a predeterminedreference) of the subject. In varying examples, each user input device114 or 116 is adapted to transmit the physiologic information, thepatient symptom information or the posture information to a processor140 (FIG. 3).

FIG. 2 is a schematic view illustrating generally, by way of example, anIMD 102 suitable for use in a system 100 capable of detecting thepresence of thoracic fluid and determining the presence of one or acombination of: a pleural effusion indication and a pulmonary edemaindication. The exemplary IMD 102 of FIG. 2 is adapted to sense athoracic impedance of a subject, which as discussed above, provides anindication of the fluid amount within the subject's thorax. In thisexample, IMD 102 is coupled to the heart 112 using one or more leadwires108, such as a multi-electrode leadwire. In this example, leadwire 108includes a tip electrode 118, a distal ring electrode 120, and aproximal ring electrode 122, each of which is disposed in the right sideof heart 112. In this example, each of the tip electrode 118, the distalring electrode 120, and the proximal ring electrode 122 is independentlyelectrically connected to a separate corresponding electricallyconductive terminal within an insulating header 124. The header 124 isaffixed to a hermetically sealed housing 126, which may be formed from aconductive metal, such as titanium. In this example, the housing 126carries various electronic components of IMD 102. The housing 126 mayadditionally house or communicate with at least one implantable device.The housing 126 may be substantially covered over its surface by asuitable insulator, such as silicone rubber. In this example, the header124 includes a header electrode 128, and the housing 126 includes ahousing electrode 130.

In one example, a thoracic impedance measurement circuit senses athoracic impedance signal by delivering a test current between: (1) atleast one of the ring electrodes 120 or 122, and (2) the housingelectrode 130; and a resulting responsive voltage is measured across thetip electrode 118 and the header electrode 128. When IMD 102 isimplanted at some distance away from the heart 112 (e.g., pectorally),this electrode configuration injects the test current over a substantialportion (but possibly not the entire portion) of the subject's thorax,such that when the resulting voltage measurement is divided by the testcurrent magnitude, it yields an indication of thoracic impedance. Usingdifferent electrodes for delivering the current and for measuring theresponsive voltage reduces the component of the measured impedancesignal that results from ohmic losses at the tissue-sense electrodeinterface and in the leadwires to the test current delivery electrodes.

While such a “four-point” probe (probe using four electrodes) is useful,it is not required. In other examples, a “three-point” probe (probeusing three electrodes, with one electrode used for both test currentdelivery and responsive voltage measurement), or a “two-point” probe(probe using two electrodes, each electrode used for both test currentdelivery and responsive voltage measurement) are used. Moreover, otherelectrode configurations could alternatively be used to implement afour-point probe. The above described four-point provides one example ofa suitable four-point probe configuration. Other illustrative examplesof four-point probe circuits for sensing thoracic impedance signals froma subject, are described in Hauck et al., U.S. Pat. No. 5,284,136entitled, “DUAL INDIFFERENT ELECTRODE PACEMAKER,” which is assigned toCardiac Pacemakers, Inc., and herein incorporated by reference in itsentirety, including its description of performing thoracic impedancemeasurements.

FIG. 3 is a schematic diagram illustrating generally, by way of example,portions of a system 100 capable of detecting the presence of thoracicfluid and determining the existence of one or a combination of: apleural effusion indication and a pulmonary edema indication. FIG. 3illustrates one conceptualization of various modules, devices, andcircuits, which are implemented either in hardware or as one or moresequences of steps carried out on a microprocessor or other controller.Such modules, devices, and circuits are illustrated separately forconceptual clarity; however, it is to be understood that the variousmodules, devices, and circuits of FIG. 3 need not be separatelyembodied, but may be combined or otherwise implemented, such as insoftware or firmware.

In one example, the system 100 differentiates pleural effusion andpulmonary edema using, in addition to sensed thoracic impedance,physiologic information (e.g., a deemed indication of one or morerespiratory sounds), patient symptoms (e.g., a deemed presence orseverity of pleuritic chest pain or a deemed intensity or frequency ofone or more hiccups), or posture information (e.g., a subject's thoracicorientation). Using the physiologic information, the patient symptominformation, or the posture information, the system 100 may also adjusta detection threshold of thoracic fluid detection (thereby adjusting asensitivity or specificity of system 100). The detection thresholdrefers to the threshold of a detection scheme at which the condition(s)a user desires to detect or treat is declared to be present. In thisexample, the system 100 includes a hermetically sealed IMD 102 and atleast one programmer or other external user interface 104 or 106. Invarying examples, the at least one external user interface 104 or 106includes a user input device 114 or 116, as discussed above. In thisexample, an intracardiac leadwire 108 connects IMD 102 with a subject'sheart 112.

The example of FIG. 3 includes a thoracic impedance test energy deliverycircuit 132 that, together with a thoracic impedance measurement circuit134, senses a thoracic impedance signal from the subject. In accordancewith instructions provided by a controller 136, an electrodeconfiguration multiplexer 138 couples the thoracic impedance test energydelivery circuit 132 and the thoracic impedance measurement circuit 134to one or more appropriate electrodes associated with the subject'sthorax. By way of such electrodes, the thoracic impedance measurementcircuit 134 may accurately sense a thoracic impedance signal from thesubject. In this example, the multiplexer 138 is coupled to a therapycircuit 141, such as a pulse delivery circuit, for delivering therapy(e.g., pacing, resynchronization, ATP, cardioversion, or defibrillation)by way of one or more electrodes 118, 120, or 122. In one example,therapy is provided to the subject in response to instructions providedby the controller 136 and received by the therapy circuit 141. Inanother example, a timing circuit 162 is used in the delivery of thetherapy to the subject.

Other illustrative examples of electrode configurations and circuits forsensing thoracic impedance signals from a subject, are described inHartley et al., U.S. Pat. No. 6,076,015 entitled, “RATE ADAPTIVE CARDIACRHYTHM MANAGEMENT DEVICE USING TRANSTHORACIC IMPEDANCE,” which isassigned to Cardiac Pacemakers, Inc., and herein incorporated byreference in its entirety, including its description of performingthoracic impedance measurements. The Hartley et al., U.S. Pat. No.6,076,015, uses thoracic impedance signals to obtain respirationsignals. In contrast, the present systems, devices, and methodsdescribed herein use thoracic impedance signals to obtain an indicationof a fluid amount within the subject's thorax; however, both thoracicfluid amount and respiration signals are obtainable using the thoracicimpedance measurement techniques described in Hartley et al. In oneexample of the present systems, devices, and methods, the thoracic fluidamount is obtained from a lower frequency (e.g., a “near-DC” (less than0.05 Hz)) portion of the thoracic impedance signal rather than thefrequencies of the respiration signal described in Hartley et al.

In this document, the near-DC component of the thoracic impedance signalrefers to the frequencies below which respiration and cardiaccontractions significantly influence the thoracic impedance signal(e.g., at least a factor of two lower than the respiration component).In one example, the near-DC component of the thoracic impedance signalrefers to signal frequencies below a cutoff frequency having a value ofabout 0.05 Hz, such as at signal frequencies from 0 Hz to about 0.05 Hz(inclusive), because the cardiac stroke and respiration components ofthe thoracic impedance signal lie at higher frequencies. Noteworthy isthat near-DC frequencies include DC frequency.

In varying examples of the system 100, the controller 136 may include aprocessor 140 or any other means capable of sequencing through variouscontrol states and having executable instructions stored in anassociated memory storage device, a microsequencer, or a state machine.In the illustrative example of FIG. 3, the controller 136 includes aprocessor 140. In one example, the processor 140 performs any filteringor other signal processing needed to extract the near-DC component fromthe sensed thoracic impedance signal by processing a stored sequence ofexecutable instructions. In this example, the filtering or signalprocessing is performed by dedicated filtering hardware (e.g., afrequency selective filter circuit 144 coupled to the processor 140). Inyet another example, the filtering or signal processing is performed inan external device such as an external user interface 104 or 106.Although the processor 140 is illustrated as being integrated within theIMD 102 in FIG. 3, the processor 140 or other sequencing means may alsobe located external to the IMD 102, such as being integrated with one ormore external user interface 104 or 106.

As discussed above, variations in how much fluid is present in asubject's thorax can take various forms and can have different causes.Beyond pleural effusion, pulmonary edema, and eating salty foods forexample, posture changes may also affect an amount of fluid the subjecthas in their thorax. As an example, moving from a supine to a standingposition can shift intravascular fluid away from the subject's thoraxtoward the subject's lower extremities thereby decreasing the amount ofthoracic fluid present. For this reason, the system 100 of FIG. 3includes a posture sensor 146 adapted to sense the subject's postureorientation. In one example, the posture sensor 146 senses a “posturesignal” which is indicative of the subject's then-current posture. Adifferent posture signal is provided for different postures (e.g., aposture signal for upright postures differs from a posture signal forrecumbent postures). One example of a suitable posture sensor 146commercially available is a two-axis accelerometer, such as Model No.ADXL202E, manufactured by Analog Devices, Inc. of Norwood, Mass., USA;however, other posture sensors may also be used without departing fromthe scope of the present systems, devices, and methods.

In this example, the posture signal sensed by the posture sensor 146 isused to remove a posture component from the sensed thoracic impedancesignal resulting in a “posture-compensated” thoracic impedance signal.In one example, a posture compensation module 148 may be used to removethe posture component using the posture signal corresponding to thethen-current posture sensed by the posture sensor 146. For example, theposture compensation module 148 may numerically increase a sensedthoracic impedance signal value when the posture sensor 146 senses thesubject's then-current posture as being supine. The rationale being thatthe subject's supine orientation may have affected the amount of fluidin the subject's thorax and thus, the sensed thoracic impedance signalvalue. The timing circuit 162 may be used to assign each sensed thoracicimpedance signal to the then-current posture signal. For instance, inthis example the timing circuit 162 is used in conjunction with memory142 to store a thoracic impedance signal sensed at time 1 with a posturesignal sensed at time 1, a thoracic impedance signal sensed at time 2with a posture signal sensed at time 2, . . . , a thoracic impedancesignal sensed at time N with a posture signal sensed at time N.

The thoracic impedance signal sensed may also be affected by confoundingfactors other than the amount of fluid present in the thorax. One suchconfounding factor is any change in blood resistivity. Blood resistivitychanges as a function of hematocrit in the blood. The hematocrit (Ht) orpacked cell volume (PCV) is the proportion of blood that is occupied byred blood cells. It is typically between 0.35 and 0.52, and is slightlyhigher, on average, in males than in females. For example, when thesubject is dehydrated, there will be less fluid in the subject's blood.Therefore, the subject's hematocrit level will increase, that is, thesubject's blood will include a higher percentage of other components,such as insulative red blood cells. This will increase the bloodresistivity, which, in turn may affect the sensed thoracic impedancesignal even though it is not necessarily associated with theextravascular fluid accumulation of pleural effusion or pulmonary edema.Other factors that are believed to possibly influence blood resistivityinclude the subject's electrolyte level, certain medications in theblood, proteins in the blood, or blood gas concentrations.

As an illustrative example, the above change in hematocrit percentagefrom 35% to 52% may correspond to a change in resistivity from about 140Ω·cm to about 200 Ω·cm. Such changes in blood resistivity may influencethe sensed thoracic impedance. This may confound thoracic fluid amountdetermination using the sensed thoracic impedance, unless theextravascular thoracic fluid amount determination is corrected for suchvariations in blood resistivity, if any.

Accordingly, the system in FIG. 3 illustrates a blood impedancemeasurement circuit 135. The blood impedance measurement circuit 135receives a blood impedance measurement from electrodes that areassociated with blood (and preferably blood in the thorax) such as inresponse to a delivery of test energy by a blood impedance test energydelivery circuit 137. In one example, the blood impedance measurementcircuit 135 and the blood impedance test energy delivery circuit 137 areconfigured similar to the thoracic impedance measurement circuit 134 andthe thoracic impedance test energy delivery circuit 132, respectively,as discussed above, except for being connected to different electrodes.Using the blood impedance measurement, the controller 136 executes asequence of instructions to compute a blood resistivity correction 145.In this example, the blood resistivity correction 145 is applied to thesensed thoracic impedance signal that is received by the processor 140.This yields a “blood resistivity-compensated” thoracic impedance signal.

In FIG. 3, the thoracic impedance test energy delivery circuit 132 isillustrated separately from the blood impedance test energy deliverycircuit 137 to assist the reader's conceptualization. In practice, thesecircuits, or portions thereof, may be combined. The combined circuit maybe coupled to different electrodes for delivering the thoracic impedancetest energy than for delivering the blood impedance test energy.Similarly, in FIG. 3, the thoracic impedance measurement circuit 134 isillustrated separately from the blood impedance measurement circuit 135to assist the reader's conceptualization. In practice, these circuits,or portions thereof, may be combined. The combined circuit may becoupled to different electrodes for measuring the responsive voltagesfor the thoracic and blood impedance measurements. Illustrative examplesof performing such thoracic and blood impedance measurements aredescribed in Stahmann et al., U.S. patent application Ser. No.10/921,503, entitled “THORACIC IMPEDANCE DETECTION WITH BLOODRESISTIVITY COMPENSATION,” which is assigned to Cardiac Pacemakers,Inc., and herein incorporated by reference in its entirety.

Once established, the sensed thoracic impedance signal or variationthereof (e.g., near-DC thoracic impedance signal, posture-compensatedthoracic impedance signal, or blood resistivity-compensated thoracicimpedance signal) may be compared to a thoracic impedance thresholdvalue to determine whether such thoracic impedance signal is“significant.” In the example of FIG. 3, a comparator 160 compares thesensed thoracic impedance signal or variation thereof to a thoracicimpedance threshold. A significant thoracic impedance signal is a signalindicative of the presence of thoracic fluid. In this example, asdiscussed above, a reduction in a thoracic impedance signal indicatesthe presence of an increase in thoracic fluid. It follows that asignificant thoracic impedance signal is a signal whose value isnumerically less than, or substantially equal to, a thoracic impedancethreshold value.

In one example, the thoracic impedance threshold is a base thoracicimpedance threshold value. The base thoracic impedance threshold valueis a thoracic impedance boundary established to differentiate betweenthoracic impedance signals that are significant (e.g., indicative of thepresence of excessive thoracic fluid) and impedance signals that arenon-significant (e.g., not indicative of the presence of excessivethoracic fluid). As an example, a thoracic impedance signal or variationthereof that is numerically less than, or substantially equal to, thebase thoracic impedance threshold indicates the presence of excessivethoracic fluid. Conversely, a thoracic impedance signal that isnumerically greater than the base thoracic impedance threshold indicatesthat no excessive thoracic fluid amount is present and the processrepeats (e.g., a thoracic impedance signal is sensed and again comparedto the base thoracic impedance threshold). In this example, the basethoracic impedance threshold is subject-specific (e.g., individualizedto the patient) and determined by a caregiver, such as at the time ofimplantation. In another example, the base thoracic impedance thresholdis nonsubject-specific (e.g., a standardized threshold). In thisexample, the base thoracic impedance threshold is programmed into systemthe 100, such as the processor 140.

In another example, the thoracic impedance threshold is an adjustedthoracic impedance threshold value which represents a change in asensitivity or specificity to the detection of the presence of thoracicfluid over the base thoracic impedance threshold. The adjusted thoracicimpedance threshold value is generated from the base thoracic impedancethreshold in addition to information collected or sensed by aphysiologic/patient symptom/posture information device 158. As anexample, information collected or sensed by device 158 that isindicative of the presence of (excessive) thoracic fluid results in theadjusted thoracic impedance threshold being numerically increased fromthe base thoracic impedance value. In a similar manner, but numericallyopposite, information received or sensed by device 158 that points awayfrom the presence of (excessive) thoracic fluid decreases (or leavesunchanged) the thoracic impedance threshold from the base thoracicimpedance value. In this example, a threshold adjustment module 164computes the adjusted thoracic impedance threshold value using theinformation collected or sensed by device 158.

In another example, although not illustrated, the sensed thoracicimpedance signal or variation thereof is changed using the informationcollected or sensed by physiologic/patient symptom/posture informationdevice 158. As an example, information received or sensed by device 158that points toward the presence of (excessive) thoracic fluid decreasesthe sensed thoracic impedance signal value. Conversely, informationreceived or sensed by device 158 that points away from the presence of(excessive) thoracic fluid increases (or leaves unchanged) the sensedthoracic impedance signal value.

Comparing the sensed thoracic impedance signal or variation thereof tothe base or adjusted thoracic impedance threshold value provides anindication of whether thoracic fluid present in the subject issignificant and thus requiring attention. In the example of FIG. 3, abinary indication at node 166 controls a therapy control module 168 thatresponsively adjusts or initiates a therapy to the subject, such ascardiac rhythm management therapy or drug therapy (e.g., diuretic). Inone example, the therapy control module 168 is integrated within IMD102. In another example, the therapy control module 168 is locatedexternally to IMD 102, such as integrated with an externaluser-interface 104 or 106. In this example, the binary indication atnode 166 is provided to a communication circuit 150, which is capable ofcommunicating to the subject or other user, via external user interface104 or 106, information about whether any significant thoracic fluidamount is present.

In this example, the system 100 includes the physiologic/patientsymptom/posture information device 158 to collect information for use indifferentiating pleural effusion and pulmonary edema or to increase asensitivity or specificity of thoracic fluid detection. If, and when, asignificant thoracic impedance is recognized, the processor 140 executesinstructions to detect one or both of: a pleural effusion indication anda pulmonary edema indication using the information acquired by thedevice 158. In the example of FIG. 3, the physiologic/patientsymptom/posture device 158 includes one or a combination of: an externalsensor 154, an external user interface 104 (which is typically nearby)including user input device 114, an external communication repeater 152,an Internet connection 110, an electronic medical database 107, anexternal user interface 106 including user input device 116 (which istypically distant), one or more implantable sensors 156 including theposture sensor 146, and a communication circuit 150.

The physiologic/patient symptom/posture information device 158 shown isadapted to collect information from a user or sense informationinternally via sensor 156 or externally via sensor 154 and provide suchinformation to the IMD 102. In one example, input device 158 is aphysiologic information device to collect physiologic information aboutthe subject and provide such information to system 100. The physiologicinformation collected by the system 100 may include a dullness orflatness of at least one respiratory sound. In another example, device158 is a patient symptom information device to collect patient symptominformation about the subject and provide such information to system100. As an example, the patient symptom information collected mayinclude the presence, absence, or severity of a pleuritic chest pain orthe presence, absence, or intensity of one or more hiccups. In yetanother example, device 158 is a posture information device to receiveposture information of the subject and provide such information tosystem 100. As an example, the posture information collected by thesystem 100 may include a posture orientation relative to a predeterminedposture reference (e.g., number of degrees the subject's thoracic cavityis inclined form a horizontal reference).

In the example of FIG. 3, the IMD 102 carries various electricalcomponents, such as the communication circuit 150, which is capable ofwirelessly communicating with a communication circuit of the externaluser interface 104. In another example, the communication circuit 150wirelessly communicates with a communication circuit of (distant)external user interface 106 by way of nearby communication repeater 152.In this example, the repeater 152 is coupled to the external userinterface 106 by way of Internet connection 110. Also in this example,the communication circuit 150 of IMD 102 is communicatively coupled to acommunication circuit of the external sensor 154. The IMD 102 mayadditionally or alternatively include the implantable sensor 156therewithin or implanted nearby and coupled thereto.

In varying examples, the system 100 includes at least one memory 142that is capable of storing information collected or sensed by device 158(e.g., physiologic information, patient symptom information, posturesignal(s)), the thoracic impedance measurement circuit 134, or the bloodimpedance measurement circuit 135. In the example of FIG. 3, the memory142 is capable of storing one or a combination of: a sensed thoracicimpedance signal, a near-DC thoracic impedance signal, aposture-compensated thoracic impedance signal, a bloodresistivity-compensated thoracic impedance signal, physiologicinformation, patient symptom information, and posture information. Inthis example, the memory 142 is also adapted to store weights (e.g.,Weight 1, Weight 2, . . . , Weight N). Each weight corresponds to a typeof information collected by device 158, such as a pitch of a respiratorysound, a presence of pleuritic chest pain, a severity of pleuritic chestpain, a presence of one or more hiccups, an intensity of one or morehiccups, a frequency of one or more hiccups, or a change in thoracicimpedance with a change in posture orientation relative to a reference.Each weight may be numerically different, such as the numericallygreatest weight may correspond to a type of information collected bydevice 158 which points towards a greatest likelihood of (e.g., havingthe strongest correlation with) a pleural effusion indication. In asimilar manner, the numerically lowest weight may correspond to a typeof information collected which points towards the least likelihood of(e.g., having the weakest correlation with) a pleural effusionindication. In another example, one or more of the weights are used inone or more algorithms to differentiate pleural effusion and pulmonaryedema or to increase a sensitivity or specificity of the presence ofthoracic fluid detection. In yet another example, the weights areobtained from historical information of one or more subjects previouslyfound to have experienced pleural effusion. In such an example, thehistorical information is stored in the electronic medical database 107coupled to Internet connection 110.

In the example of FIG. 3, a differentiation module 169 is adapted todifferentiate pleural effusion and pulmonary edema. Such differentiationmay use one or a combination of: the physiologic information, thepatient symptom information, and the posture information. In oneexample, the differentiation module 169 weights (e.g., Weight 1, Weight2, . . . , Weight N) one or more of: the physiologic information, thepatient symptom information, and the posture information whendifferentiating pleural effusion and pulmonary edema.

FIG. 4 is a flow chart including factors for differentiating pleuraleffusion and pulmonary edema once a significant thoracic impedance isrecognized (e.g., a thoracic impedance signal value less than, orsubstantially equal to, a thoracic impedance threshold value). In theexample of FIG. 4, a thoracic impedance signal (Z) is shown thatgenerally decreases as time (t) increases. As discussed above, thisindicates the amount of thoracic fluid present in a subject isincreasing. The thoracic impedance signal crosses a thoracic impedancethreshold value between t₁₀₇ and t₁₀₈. In this example, the crossing ofthe thoracic impedance threshold denotes that a significant amount offluid is present in the subject's thorax, which may be the result of oneor both of: pleural effusion and pulmonary edema.

The present systems, devices, and methods allow physiologic information,patient symptom information, and posture information to be collected orsensed and processed to differentiate pleural effusion and pulmonaryedema. As an example, the present systems, devices, and methods use oneor a combination of: at least one respiratory sound 170 (physiologicinformation), a pleuritic chest pain 172 (patient symptom information),one or more hiccups 174 (patient symptom information), and a rate ofchange in thoracic impedance with a change in posture 178 (postureinformation) to differentiate pleural effusion from pulmonary edema.

In one example, a subject's respiratory sound 170 is used todifferentiate pleural effusion and pulmonary edema. In one example, theat least one respiratory sound 170 is measured by an implantable sensor156, which includes a microphone, accelerometer, or other like sounddetector. In another example, a caregiver listens to the sound of thesubject's breathing with a stethoscope (or other external sounddetector) and may further tap on the subject's chest to listen fordullness. This act or technique is sometimes simply referred to as“percussion.” When listening to the subject's breathing and tapping onthe subject's chest, the caregiver typically does so in a symmetricalmanner (e.g., first listens to the left side, then listens to the rightside in approximately the same location to determine if any differencein sound exists). Whether the at least one respiratory sound 170 issensed by implantable sensor 156 or detected by a caregiver, anindication of the sound ascertained is communicated to the processor140. In the latter case, the indication is entered into external userinterface 104 or 106 of the physiologic/patient symptom/posture device158. A flat or dull sound resulting from the percussion points toward apleural effusion detection; while, a wheeze or sharp sound is typicallyassociated with pulmonary edema. In one example, a pleural effusiondetection is differentiated from a pulmonary edema detection using, atleast in part, one or more respiratory sound.

In another example, a subject's pleuritic chest pain 172 is used todifferentiate pleural effusion and pulmonary edema. In one example, thesubject enters an indication of an intensity of the pleuritic chest pain(e.g., a number on a scale of 1-10, with “10” being greatest pain) intoexternal user interface 104 or 106. In another example, the caregiverexamines the subject, such as by performing a lung scan, an x-ray of thesubject's chest, or questioning of the subject, and thereafter enters adeemed indication of the pleuritic chest pain into external userinterface 104 or 106. Although there are many possible underlying causesand intensities of pleuritic chest pain, which may not be the result ofpleural effusion (e.g., underlying cause may be other problemsassociated with the heart, lungs, esophagus, muscles, ribs, tendons, ornerves), pleuritic chest pain in conjunction with a significant thoracicimpedance signal correlates to an indication of pleural effusion. On theother hand, pleuritic chest pain 172 is typically not associated withpulmonary edema. One rationale for the association between pleuriticchest pain and pleural effusion is that the abnormal buildup of fluidaround the lungs (which is present in pleural effusion) may press on thelungs, making it difficult for the subject's lungs to fully expand. Insome situations, part or all of the lung will collapse. This collapseoften causes pleuritic chest pain. The pleuritic chest pain ishistorically described by subjects as sharp or stabbing and isexacerbated with deep inhalation. In one example, pleural effusion isdifferentiated from pulmonary edema using, at least in part, anypresence of pleuritic chest pain.

In another example, a subject's hiccups 174 are used to differentiatebetween pleural effusion and pulmonary edema. In one example, a userenters an indication of the presence, intensity, frequency, or durationof one or more hiccups (e.g., a number on a scale of 1-10, with “10”being one or a combination of: high presence, intensity, frequency, andduration of the hiccups) into external user interface 104 or 106. Inanother example, the caregiver examines the subject, such as byquestioning the subject regarding the one or more hiccups in detail andenters a deemed indication of the severity of the subject's hiccups intoexternal user interface 104 or 106. As an example, the caregiver may askthe subject questions regarding the time pattern of the hiccups, suchas: (1) Do you get hiccups easily?, or (2) How long has the currentepisode of hiccups lasted? In another example, the caregiver may ask thesubject questions regarding possible aggravating factors of the hiccups,such as: (1) Have you recently consumed something that was either hot orspicy? (hot and spicy foods or liquids may be a cause of hiccups), (2)Have you recently consumed carbonated beverages? (carbonation may be acause of hiccups), or (3) Have you recently been exposed to any fumes?(noxious fumes may be a cause of hiccups). In another example, thecaregiver may ask the subject questions regarding relieving factors,such as: (1) What have you done to try to relieve the hiccups?, (2) Whathas been effective for you in the past?, (3) How effective was theattempt at home treatment (e.g., holding breath, breathing repeatedlyinto a paper bag, drinking a glass of cold water, or eating a teaspoonof sugar)?, or (4) Did the hiccups stop for a while and then restart? Inanother example, the caregiver may ask the subject, or examine thesubject, to determine what other symptoms are present in addition tohiccups 174. In yet another example, the one or more hiccups aremeasured by an implantable sensor 156, which includes a microphone,accelerometer, or other sound or vibration detector and automaticallycommunicated to the processor 140.

A hiccup is a sound produced by an unintentional movement of the muscleat the base of the lungs, a location also commonly referred to as the“diaphragm,” followed by rapid closure of the vocal chords. Althoughhiccups may be caused by noxious fumes, hot and spicy foods or liquids,tumor(s) affecting the “hiccup center” in the brain, or abdominalsurgery; hiccups in conjunction with a significant thoracic impedancesignal, points towards an indication of pleural effusion. On the otherhand, hiccups are typically not associated with pulmonary edema. Onerationale for the association between hiccups and pleural effusion isthat hiccups may be the result of an irritation of the nerves thatcontrol the diaphragm. Such irritation may be due to lung inflammation.The normally smooth pleural surfaces, which are now roughened by theinflammation, rub together with each breath. As a result, fluid mayaccumulate at the site of the pleural inflammation. As mentioned above,pleural effusion is the abnormal fluid accumulation outside of thelungs. In one example, pleural effusion is differentiated from pulmonaryedema using, at least in part, the presence of one or more hiccups.

In another example, a subject's rate of change in thoracic fluid with achange in posture orientation is used to differentiate pleural effusionand pulmonary edema. In one example, the subject's posture 178 ismeasured by a posture sensor 146. In another example, an indication ofthe subject's posture 178 is entered into external user interface 104 or106 by a user. As an example, the indication of the subject's posture178 is an inclination amount (e.g., approximate degree incline) from areference (e.g., horizontal reference). Thoracic fluid outside of thelungs (associated with pleural effusion) shifts faster than fluid insideof the lungs (associated with pulmonary edema) when posture changes.Thus, when a rapid change in impedance occurs with a change in posture,such rapid change points toward an indication of pleural effusion andaway from an indication of pulmonary edema.

FIG. 4 combines a significant thoracic fluid detection (e.g., thoracicimpedance signal value less than, or substantially equal to, a thoracicimpedance threshold value) with one or a combination of: at least onerespiratory sound 170, a pleuritic chest pain 172, one or more hiccups174, and a thoracic impedance change with a change in posture 178 todetect a pleural effusion indication 166. The above discusseddifferentiation factors 170-178 are not meant to be exhaustive, and mayinclude other physiological information, other patient symptoms, orother posture information to differentiate pleural effusion andpulmonary edema.

An IMD's detection scheme is typically characterized by its“sensitivity” and “specificity.” As discussed above, sensitivitygenerally refers to the ability of the detection scheme to effectivelydetect that which the caregiver desires the IMD to detect or treat;while specificity generally refers to the ability of the detectionscheme to avoid improperly detecting or treating that which thecaregiver determines that the device should not treat. Ideally, an IMDwould have both 100% sensitivity and 100% specificity. However, forpractical IMDs, there exists a tradeoff between sensitivity andspecificity.

As discussed above, early detection of the presence of thoracic fluidmay reduce or eliminate the need for hospital admission of a subjectwith heart failure. Therefore, it may be desirable to increasesensitivity of thoracic fluid detection beyond what can be obtained froma device that merely senses thoracic impedance. For a given detectionsystem, this results in reduced specificity due to the tradeoff betweensensitivity and specificity (discussed above). If specificity is reducedtoo much, the detector may give many spurious detections resulting inthe user no longer trusting in its accuracy. Therefore, the presentsystems, devices, and methods are intended to provide increasedsensitivity of thoracic fluid detection for a given level ofspecificity, as illustrated in FIG. 5. Alternatively, the presentsystems, devices, and methods may be used to provide improvedspecificity for a given level of sensitivity, or some combinedsimultaneous improvement of both sensitivity and specificity.

FIG. 5 is a graph illustrating an increase in sensitivity of the presentsystems, devices, and methods which detect the presence of thoracicfluid in a subject. The increase in sensitivity of detection may providea detection lead time and thus, alert a user of a significant thoracicfluid amount sooner than a lower sensitivity system would provide. Asdiscussed above, as fluid accumulation in the thorax of a subjectincreases, thoracic impedance decreases. Conversely, as fluid in thethorax depletes, thoracic impedance increases. Typically, a thoracicimpedance signal includes cardiac stroke, respiration, posture, or bloodresistivity components. Thus, in some examples, the thoracic impedancesignal used in comparison to a thoracic impedance threshold is obtainedby filtering or compensating the thoracic impedance signal to obtain anear-DC, posture-compensated, or blood resistivity-compensated thoracicimpedance signal, respectively. In this example, a near-DC component ofthe thoracic impedance signal refers to signal frequencies below acutoff frequency having a value of about 0.05 Hz, such as at signalfrequencies from 0 Hz to about 0.05 Hz, because the cardiac stroke andrespiration components of the thoracic impedance signal lie at higherfrequencies (e.g., >about 0.05 Hz). In another example, a posturecompensation module 148 compensates the thoracic impedance signal using,in part, a posture signal provided by a posture sensor 146. In yetanother example, the thoracic impedance signal is adjusted to compensatefor changes in blood resistivity. In the illustrative example of FIG. 5,a near-DC thoracic impedance signal is graphed versus time.

In one example, the system 100 recognizes a significant thoracic fluidamount by comparing the near-DC thoracic impedance signal value to abase thoracic impedance threshold value. If, and when, the near-DCthoracic impedance signal value is less than, or substantially equal to,the base thoracic impedance threshold value, the subject, caregiver, orother user is alerted that a significant thoracic fluid amount ispresent; thus, indicating the possible presence of one or both of:pleural effusion and pulmonary edema. In the example of FIG. 5, thenear-DC thoracic impedance signal (Z) crosses the base thoracicimpedance threshold (Threshold_(Base)) at time t_(Base).

The system 100 enhances the detection of thoracic fluid using, inaddition to the sensed, filtered, or compensated thoracic impedance,information collected or sensed by physiologic/patient symptom/postureinformation device 158 to adjust the base thoracic impedance threshold,resulting in Threshold_(Adjusted). In one example, information collectedor sensed by device 158 that is indicative of the presence of thoracicfluid results in the adjusted thoracic impedance threshold value beingnumerically increased from the base thoracic impedance value. In asimilar manner, but numerically opposite, information collected orsensed by device 158 that points away from the presence of thoracicfluid decreases (or leaves unchanged) the thoracic impedance thresholdfrom the base thoracic impedance value. As an example, suppose device158 collects or senses information from the subject including: flat ordull respiratory sounds, an indication of high intensity pleuritic chestpain, an indication of a high frequency of hiccups, and a large rate ofchange in thoracic impedance with a change in posture. As discussedabove, such information is indicative of the presence of thoracic fluid(specifically, points toward the presence of pleural effusion).Accordingly, a numerically increased threshold from Threshold_(Base) toThreshold_(Adjusted) results. In the example of FIG. 5, the near-DCthoracic impedance signal (Z) crosses a Threshold_(Adjusted) at timet_(Adjusted), resulting in a timely alert to the subject or caregiver.As shown, Threshold_(Adjusted) results in an earlier (by Δt) alertcompared to Threshold_(Base). Although the foregoing example includedthe comparison of a near-DC thoracic impedance signal to a base oradjusted thoracic impedance threshold, the present systems, devices, andmethods are not so limited. The use of a non-filtered, non-compensated(e.g., sensed) thoracic impedance signal, a posture-compensated thoracicimpedance signal, or a blood resistivity-compensated thoracic impedancesignal is also within the scope of the present systems, devices, andmethods.

FIG. 6 is a flow chart illustrating one method of detecting the presenceof thoracic fluid in a subject and determining the presence of one orboth of: pleural effusion and pulmonary edema. The present method sensesthe presence of thoracic fluid and determines the cause of such thoracicfluid accumulation (e.g., pleural effusion or pulmonary edema). At 180,a thoracic impedance signal is sensed. This may be accomplished in anumber of ways. In one example, a thoracic impedance signal is measuredby delivering a test current between: (1) at least one ring electrode120 or 122; and (2) a housing electrode 130, and a resulting responsivevoltage is measured across a tip electrode 118 and a header electrode128. In another example, the delivering the test current includesinjecting a four-phase carrier signal, such as between the housingelectrode 130 and one of the ring electrodes 120 or 122. In one suchexample, the first and third phases use +320 microampere pulses that are20 microseconds long. The second and fourth phases use −320 microamperepulses that are also 20 microseconds long. The four phases are repeatedat 50 millisecond intervals to provide a test current signal from whicha responsive voltage may be measured.

At 182, the sensed thoracic impedance signal or variation thereof (e.g.,near-DC thoracic impedance signal or blood resistivity-compensatedthoracic impedance signal) is compensated for posture. There are anumber of ways in which this can be accomplished. In one example, thesystem 100 includes a posture sensor 146 and a posture compensationmodule 148. The posture sensor 146 provides a posture signal indicatinga subject's then-current posture. The posture compensation module 148compensates the sensed thoracic impedance signal using the posturesignal. For instance, if a posture signal indicates a subject is in asupine orientation, the posture compensation module 148 may increase thesensed thoracic impedance signal since the supine orientation may havedecreased the thoracic impedance signal sensed (indicating an increasein thoracic fluid), as discussed above.

At 183, the sensed thoracic impedance signal or variation thereof (e.g.,posture-compensated thoracic impedance signal or near-DC thoracicimpedance signal) is compensated for blood resistivity. There are anumber of ways in which this can be accomplished. In one example, theblood impedance measurement is performed in the same manner as thethoracic impedance measurement (discussed above), except thatmeasurement of the responsive voltage is across two electrodes that areboth typically located in the same chamber of the subject's heart 112 orsame blood vessel. Once measured, the controller 136, using the bloodimpedance measurement, executes a sequence of instructions to compute ablood resistivity correction 145. This blood resistivity correction 145can then be applied to the sensed thoracic impedance or variationthereof that is received by processor 140. Illustrative examples ofcompensating the thoracic fluid indication for blood resistivity aredescribed in Stahmann et al., U.S. patent application Ser. No.10/921,503, entitled “THORACIC IMPEDANCE DETECTION WITH BLOODRESISTIVITY COMPENSATION,” which is assigned to Cardiac Pacemakers,Inc., and herein incorporated by reference in its entirety, includingits equations for representing the blood resistivity-compensatedthoracic impedance signal. In one example, the sensed thoracic impedancesignal is compensated for blood resistivity at 183 before beingcompensated for posture at 182.

At 184, the sensed thoracic impedance signal or variation thereof (e.g.,posture-compensated thoracic impedance signal or bloodresistivity-compensated thoracic impedance signal) is filtered. Thisresults in a near-DC thoracic impedance signal. The filtering may beaccomplished in a number of ways. In one example, a processor 140 of thesystem 100 performs any filtering or other signal processing needed toextract from the thoracic impedance signal a near-DC component. Inanother example, a frequency selective filter circuit 144 performs anyfiltering or other signal processing needed to extract from the thoracicimpedance signal a near-DC component. In another example, the sensedthoracic impedance signal is filtered at 184 to obtain a near-DCthoracic impedance signal before being compensated for posture at 182.In yet another example, the sensed thoracic impedance signal is filteredat 184 to obtain a near-DC thoracic impedance signal before beingcompensated for blood resistivity at 183.

At 186, the near-DC thoracic impedance signal, the posture-compensatedthoracic impedance signal, or the blood resistivity-compensated thoracicimpedance signal is compared to a base thoracic impedance thresholdvalue. As discussed above, the base thoracic impedance threshold valuedefines a boundary between a significant thoracic fluid amount and aninsignificant thoracic fluid amount. In one example, the comparisonincludes determining whether the near-DC thoracic impedance signal isless than, or substantially equal to, the base thoracic impedancethreshold value. Where the near-DC thoracic impedance is greater thanthe base thoracic impedance threshold value, a non-significantindication of thoracic fluid results at 196 and process flow returns to180. In examples where the near-DC thoracic impedance is less than, orsubstantially equal to, the thoracic impedance threshold, a significantindication of abnormal thoracic fluid accumulation results at 188.Although the foregoing included the comparison of a near-DC thoracicimpedance signal to a base thoracic impedance threshold, the presentsystems, devices, and methods are not so limited. The use of anon-filtered, non-compensated (e.g., sensed) thoracic impedance signal,posture-compensated thoracic impedance signal, or bloodresistivity-compensated thoracic impedance signal is also within thescope of the present systems, devices, and methods.

At 190, the system 100 determines whether the significant thoracic fluidamount was caused by pleural effusion or pulmonary edema or both. In oneexample, pleural effusion is differentiated from pulmonary edema usingone or a combination of: at least one respiratory sound 170, a pleuriticchest pain 172, one or more hiccups 174, and a rate of change inthoracic impedance with a change in posture 178. At 192, the systemtimely alerts the subject or the caregiver to an indication of pleuraleffusion or pulmonary edema. The alert may be provided in a number ofways. In one example, an audible tone is sounded, which prompts thesubject to call his/her caregiver. If the subject is linked to a remotemonitoring system (e.g., via a communication repeater 152), the alertcan be electronically communicated to the caregiver. In another example,the alert may be provided (e.g., displayed) to the subject or caregiverat the subject's next visit to his/her caregiver. In one example, at194, a therapy is adjusted or initiated in response to the detection ofone or both of: pleural effusion or pulmonary edema at 190. As anexample, the therapy is selected from a group consisting of: cardiacrhythm management therapy or drug therapy. Notably, the therapy providedto the subject may differ depending on whether pleural effusion orpulmonary edema or both are detected.

FIG. 7 is a flow chart illustrating one method of increasing thesensitivity of the presence of thoracic fluid detection in a subject anddetermining the existence of one or a combination of: pleural effusionand pulmonary edema. At 180, a thoracic impedance signal is sensed, suchas discussed above. At 182, the sensed thoracic impedance signal orvariation thereof is compensated for posture, as also discussed above.At 183, the sensed thoracic impedance signal or variation thereof iscompensated for blood resistivity, as also discussed above. At 184, thesensed thoracic impedance signal or variation thereof is filtered toobtain a near-DC thoracic impedance signal, as further discussed above.

At 198, physiologic information is sensed or collected. There are anumber of ways in which the physiologic information may be sensed orcollected. In one example, the physiologic information sensed orcollected includes at least one respiratory sound 170. As an example,the at least one respiratory sound 170 is measured by an implantablesensor 156, which includes a microphone, accelerometer, or other likesound detector. In another example, a caregiver listens to the sound ofthe subject's breathing with a stethoscope and may tap on the subject'schest to listen for dullness. In yet another example, the caregiver orother user enters a deemed indication of the respiratory soundascertained into an external user interface 104 or 106.

At 200, patient symptom information is sensed or collected. There are anumber of ways in which the patient symptom information can be sensed orcollected. In one example, this includes information about one or bothof: a subject's pleuritic chest pain 172 and a subject's hiccups 174. Asan example, the subject enters an indication of the intensity (e.g.,numerically) of the deemed chest pain severity into external userinterface 104 or 106. In another example, the caregiver examines thesubject, such as by performing a lung scan, an x-ray of the subject'schest, or questioning the subject, and thereafter enters a deemedindication of the chest pain severity into external user interface 104or 106. In another example, a user enters an indication (e.g.,numerically) of the presence, intensity, frequency, or duration of oneor more hiccups into external user interface 104 or 106. In yet anotherexample, the caregiver examines the subject, such as by questioning thesubject regarding the one or more hiccups in detail and enters a deemedindication of the hiccups intensity, frequency, or duration intoexternal user interface 104 or 106.

At 202, posture information associated with sensed thoracic impedance issensed or collected. There are a number of ways in which suchinformation can be sensed or collected. In one example, a subject'sposture 178 is measured by a posture sensor 146. In another example, anindication of the subject's posture 178 (e.g., approximate degreeincline over a horizontal reference) is entered into external userinterface 104 or 106 by a user.

At 204, a base thoracic impedance threshold (Threshold_(Base)) ischanged to an adjusted thoracic impedance threshold(Threshold_(Adjusted)) using one or more of: the physiologicinformation, the patient symptom information, and the postureinformation associated with thoracic impedance signals, as discussedabove.

At 206, the near-DC thoracic impedance signal, the posture-compensatedthoracic impedance signal, or the blood resistivity-compensated near-DCthoracic impedance signal is compared to an adjusted thoracic impedancethreshold value (Threshold_(Adjusted)). In one example, the adjustedthoracic impedance threshold value increases the sensitivity ofdetecting the presence of thoracic fluid. In one example, the comparisonincludes determining whether the near-DC thoracic impedance signal valueis less than, or substantially equal to, the adjusted thoracic impedancethreshold value. Where the near-DC thoracic impedance value exceeds theadjusted thoracic impedance threshold value, no significant thoracicfluid amount is deemed present at 210, the process flow then returns to180. Where the near-DC thoracic impedance value is less than, orsubstantially equal to, the adjusted thoracic impedance threshold value,a significant indication of thoracic fluid accumulation is deemedpresent at 208. Although the foregoing included the comparison of anear-DC thoracic impedance signal to an adjusted thoracic impedancethreshold, the present systems, devices, and methods are not so limited.The use of a non-filtered, non-compensated (e.g., sensed) thoracicimpedance signal, posture-compensated thoracic impedance signal, orblood resistivity-compensated thoracic impedance signal is also withinthe scope of the present systems, devices, and methods.

At 190, the system 100 determines the existence of whether thesignificant thoracic fluid amount was caused by pleural effusion orpulmonary edema, such as by using one or a combination of: at least onerespiratory sound 170, a pleuritic chest pain 172, one or more hiccups174, and a rate of change of thoracic impedance with a change in posture178. At 192, the system 100 timely alerts the subject or the caregiverto an indication of pleural effusion or pulmonary edema. The alert maybe provided in a number of ways, as discussed above. At 194, a therapyis adjusted or initiated in response to the detection of one or both of:pleural effusion and pulmonary edema at 190. As an example, the therapyis selected from a group consisting of cardiac rhythm management therapyor drug therapy. Notably, the therapy provided to the subject may differdepending on whether pleural effusion, pulmonary edema, or both aredetected.

Like pulmonary edema, pleural effusion will cause a decrease in thoracicimpedance due to an increase in thoracic fluid. Although pleuraleffusion may occur in concert with pulmonary edema, pleural effusion mayoccur alone. The present systems, devices, and methods provide fordifferentiation between pleural effusion and pulmonary edema. There arealso a number of other advantages. For example, the present systems,devices, and methods may improve a sensitivity or specificity ofdetecting the presence of thoracic fluid in a subject. The improvedsensitivity may in turn provide an earlier warning of pleural effusionor pulmonary edema as compared to a lower sensitivity system, which maybe critical to managing the subject's well-being.

As mentioned above, this Detailed Description is not to be taken in alimiting sense, and the scope of various embodiments is defined only bythe appended claims, along with the full range of legal equivalents towhich such claims are entitled. In the appended claims, the term“including” is used as the plain-English equivalent of the term“comprising.” Also, in the following claims, the terms “including” and“comprising” are open-ended, that is, a system, device, article, orprocess that includes elements in addition to those listed after such aterm in a claim are still deemed to fall within the scope of that claim.

The Abstract of the Disclosure is provided to comply with 37 C.F.R.§1.72(b), requiring an abstract that will allow the reader to quicklyascertain the nature of the technical disclosure. It is submitted withthe understanding that it will not be used to interpret or limit thescope or meaning of the claims. In addition, in the foregoing DetailedDescription, it can be seen that various features are grouped togetherin a single embodiment for the purpose of streamlining the disclosure.This method of disclosure is not to be interpreted as reflecting anintention that the claimed embodiments require more features than areexpressly recited in each claim. Rather, as the following claimsreflect, inventive subject matter lies in less than all features of asingle disclosed embodiment. Thus, the following claims are herebyincorporated into the Detailed Description, with each claim standing onits own as a separate embodiment.

1. A system for the detection of fluid in a subject, comprising: animplantable thoracic impedance measurement circuit, configured to sensea thoracic impedance signal from the subject; a processor, coupled withthe thoracic impedance measurement circuit to receive the thoracicimpedance signal, the processor configured to detect a pleural effusionindication including a differential indication of pleural effusionrelative to pulmonary edema using the thoracic impedance signal; and anexternal user interface, coupled to the processor to receive informationabout the pleural effusion indication, the external user interfaceconfigured to provide a user-detectable lung fluid indication usinginformation about the pleural effusion indication.
 2. The system ofclaim 1, comprising at least one physiologic information device coupledto the processor, the physiologic information device configured to senseor collect physiologic information about the subject.
 3. The system ofclaim 2, wherein the processor is configured to detect the pleuraleffusion indication using, at least in part, the physiologic informationabout the subject.
 4. The system of claim 3, wherein the physiologicinformation about the subject includes at least one respiratory sound.5. The system of claim 1, comprising at least one patient symptom devicecoupled to the processor, the patient symptom device configured to senseor collect patient symptom information about the subject.
 6. The systemof claim 5, wherein the processor is configured to detect the pleuraleffusion indication using, at least in part, the patient symptominformation about the subject.
 7. The system of claim 6, wherein thepatient symptom information about the subject includes one or both of anindication of pleuritic chest pain or at least one hiccup.
 8. The systemof claim 1, comprising a posture sensor coupled to the processor, theposture sensor configured to sense a posture signal indicative of thesubject's then-current orientation.
 9. The system of claim 8, whereinthe processor is configured to detect the pleural effusion indicationusing, at least in part, a rate of change in the thoracic impedancesignal associated with a change in the posture signal.
 10. The system ofclaim 1, wherein the external user interface includes a user inputdevice, the user input device configured to collect from a user one or acombination of physiologic information, patient symptom information, orposture information about the subject.
 11. The system of claim 10,wherein the external user interface is configured to transmit thephysiologic information, the patient symptom information, or the postureinformation to the processor for use in detecting the pleural effusionindication.
 12. The system of claim 1, comprising a therapy controlmodule configured to adjust or initiate a therapy using at least one ofthe pleural effusion indication or the user-detectable lung fluidindication.
 13. A method for the detection of thoracic fluid in asubject, comprising: sensing a thoracic impedance signal using animplantable device; detecting a pleural effusion indication, including adifferential indication of pleural effusion relative to pulmonary edema,using the thoracic impedance signal; deriving a user-detectable lungfluid indication using information about the pleural effusionindication; and providing the user-detectable lung fluid indication byway of an external user interface.
 14. The method of claim 13,comprising sensing or receiving physiologic information about thesubject, and using the physiologic information to detect the pleuraleffusion indication.
 15. The method of claim 14, wherein sensing orreceiving physiologic information about the subject includes sensing orreceiving at least one respiratory sound.
 16. The method of claim 13,comprising sensing or receiving patient symptom information about thesubject, and using the patient symptom information to detect the pleuraleffusion indication.
 17. The method of claim 16, wherein sensing orreceiving patient symptom information about the subject includes sensingor receiving one or both of an indication of pleuritic chest pain or atleast one hiccup.
 18. The method of claim 13, comprising sensing orreceiving a then-current posture orientation of the subject, and usinginformation about a change in the thoracic impedance signal with achange in the posture orientation to detect the pleural effusionindication.
 19. The method of claim 13, comprising filtering thethoracic impedance signal to obtain a near-DC thoracic impedance signal,and using the near-DC thoracic impedance signal to detect the pleuraleffusion indication.
 20. The method of claim 13, comprising compensatingthe thoracic impedance signal to extract a blood resistivity-influencedcomponent of the thoracic impedance signal, and using a bloodresistivity-compensated thoracic impedance signal to detect the pleuraleffusion indication.
 21. The method of claim 13, comprising providing atherapy to the subject in response to at least one of the pleuraleffusion indication or the user-detectable lung fluid indication.